Identification of a novel 12p13.3 amplicon in nasopharyngeal carcinoma
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摘要Nasopharyngeal carcinoma (NPC) is a distinct type of head and neck cancer commonly occurring in southern China. To decipher the molecular basis of this cancer, we performed high-resolution array CGH analysis on eight tumour lines and 10 primary tumours to identify the genes involved in NPC tumorigenesis. In this study, multiple regions of gain were consistently found at 1q21-q24, 7q11-12, 7q21-22., 11q13, 12p13, 12q13, 19p13 and 19q13. Importantly, a 2.1 Mb region at 12p13.31 was highly amplified in a NPC xenograft, xeno-2117. By FISH mapping, we have further delineated the amplicon to a 1.24 region flanked by RP11-319E16 and RP11-433J6. Copy number gains of this amplicon were confirmed in 21/41 (51%) primary tumours, while three cases (7.3%) showed high copy number amplification. Among the 13 genes within this amplicon, three candidate genes, lymphotoxin beta receptor (LT beta R), tumour necrosis factor receptor superfamily memeber 1A (TNFRSF1R) and FLJI0665, were specifically over-expressed in the NPC xenograft with 12p13.3 amplification. However, only LT beta R was frequently over-expressed in primary tumours. LT beta R is a member of the TNF family of receptors, which can modulate NF-kappa B signalling pathways. Over-expression of LT beta R in nasopharyngeal epithelial cells resulted in an increase of NF-kappa B activity and cell proliferation. In vivo study showed that suppression of LT beta R by siRNA led to growth inhibition in the NPC tumour with 12p13.3 amplification. These findings implied that LT beta R is a potential NPC-associated oncogene within the 12p13.3 amplicon and that its alteration is important in NPC tumorigenesis. Copyright (C) 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
著者Or YYY, Chung GTY, To KF, Chow C, Choy KW, Tong CYK, Leung AWC, Hui ABY, Tsao SW, Ng HK, Yip TTC, Busson P, Lo KW
期刊名稱Journal of Pathology
出版年份2010
月份1
日期1
卷號220
期次1
出版社JOHN WILEY & SONS LTD
頁次97 - 107
國際標準期刊號0022-3417
電子國際標準期刊號1096-9896
語言英式英語
關鍵詞12p13.3 amplicon; array CGH; Epstein-Barr virus; LT beta R; nasopharyngeal carcinoma; oncogene
Web of Science 學科類別Oncology; ONCOLOGY; Pathology; PATHOLOGY

上次更新時間 2020-26-10 於 01:12